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A B S T R A C T We have studied 17 elderly and 27 nonelderly, nonobese subjects (mean age 69±1 and 37±2 yr, respectively) to assess the mechanisms responsible for the abnormal carbohydrate tolerance associated with aging. Serum glucose and insulin levels were significantly elevated in the elderly subjects compared with the nonelderly subjects during a 75-g oral glucose tolerance test, suggesting an insulin resistant state. Peripheral insulin sensitivity was assessed in both groups using the euglycemic glucose clamp technique during an insulin infusion rate of 40

This study evaluated the long-term safety and efficacy of dapagliflozin as an adjunct to adjustable insulin in patients with type 1 diabetes and inadequate glycemic control. RESEARCH DESIGN AND METHODS DEPICT-1 (Dapagliflozin Evaluation in Patients With Inadequately Controlled Type 1 Diabetes) was a randomized (1:1:1), double-blind, placebo-controlled phase 3 study of dapagliflozin 5 mg and 10 mg in patients with type 1 diabetes (HbA 1c 7.5-10.5% [58-91 mmol/mol]) (NCT02268214). The results of the 52-week study, consisting of the 24-week short-term and 28-week extension period, are reported here. RESULTS Of the 833 patients randomized into the study, 708 (85%) completed the 52-week study. Over 52 weeks, dapagliflozin 5 mg and 10 mg led to clinically significant reductions in HbA 1c (difference vs. placebo [95% CI] 20.

Abstract. The present study was designed to quantitate the interaction between the decrease in target tissue insulin action seen in subjects with Type II diabetes and the mass action effect of glucose exerted via the prevailing hyperglycemic state. To this end, euglycemic glucose clamp studies were performed in 26 control subjects using insulin infusion rates of 15, 40, 120, 240, and 1,200 mU/M2 per min and in 10 Type II diabetic subjects using insulin infusion rates of 120 and 1,200 mU/M2 per min.The results of these euglycemic studies indicated that insulin-stimulated peripheral glucose disposal was decreased in the Type II diabetics due to a combined receptor (rightward shift in the dose-response curve) and postreceptor defect in insulin action (decreased maximal response), whereas the decrease in insulin-mediated suppression of hepatic glucose output (HGO) was consistent with a defect in insulin binding (rightward shift in dose-response curve).Hyperglycemic glucose clamp studies were also performed in the Type II diabetics at their respective fasting serum glucose levels (mean [±SE]

Aging is associated with hyperinsulinemia, but reports vary on the contributions of altered insulin clearance versus insulin secretion to this phenomenon. To elucidate the role of insulin secretion in the hyperinsulinemia of aging, 10 elderly (age 66 +/- 4 yr, body mass index 25 +/- kg/m2) and 8 young (age 30 +/- 5 yr, body mass index 24 +/- 3 kg/m2) subjects were studied to determine rates of insulin secretion in response to fasting, mixed meals, and intravenous glucose administration. Insulin secretion was determined with a two-compartment model based on individual C-peptide kinetic parameters derived after bolus injection of biosynthetic human C-peptide. Basal insulin secretion rates were increased in elderly subjects (82.5 +/- 9.0 vs. 62.8 +/- 6.1 pmol.min-1.m-2; P less than .05). This was reflected in elevated serum insulin levels in elderly subjects (62.8 +/- 10.1 vs. 41.1 +/- 5.0 pM, P less than .05). During a 24-h mixed-meal profile, elderly subjects had an increase in their glucose response (P less than .01 by analysis of variance [ANOVA]) and total insulin secretion (261 +/- 28 vs. 195 +/- 22 nmol.24 h-1.m-2; P less than .05) compared with young subjects. However, the relative total increases in both glycemia and insulin secretion, calculated as a function of basal levels, were similar between the groups (both NS). To experimentally control for differences in glycemia, both groups underwent a 16.8-mM hyperglycemic clamp and a stepped intravenous glucose infusion to match glycemia. Under these steady-state and dynamic conditions, insulin secretion profiles were nearly identical (NS by ANOVA).(ABSTRACT TRUNCATED AT 250 WORDS)